Biomedical Engineering Reference
In-Depth Information
no interest group can dominate), they follow due process (all points of view are
addressed), and they are relevant and coherent (such that they do not duplicate existing
standards) [12]. The E55 committee includes members from both brand name and
generic pharmaceutical manufacturers, biopharmaceutical and biotechnology compa-
nies, regulators, consultants, suppliers, and academia, and represents a broad base of
interests and expertise.
The use of standards is voluntary but ensures compliance if they are followed. US
government agencies, including the FDA, are mandated by law, via the National
Technology Transfer and Advancement Act of 1995 [13], to use voluntary
consensus standards in lieu of government-unique standards, except where inconsistent
with law or otherwise impractical [2]. The agency sees standards as “an optional way to
describe how a certain function will be implemented to meet requirements. FDA
describes what has to be done to meet the requirements and the companies may use
standards to describe how it is done” [14]. The benefit of this approach is that companies
can have a degree of confidence in the acceptability of certain standards or practices, and
regulators have the benefit of participation in, and oversight of, the rigor behind
the recommended practice. To date, four standards have been approved (including
new approaches to equipment verification, streamlining IQ/OQ/PQ; and continuous
verification), and over a dozen of others are in various stages of development, as given in
Table 13.1.
The standards are valuable tools for the development and implementation of modern
manufacturing practices, ensuring quality and capturing value. For example, the systems
verification standard, E2500, offers a modern approach to process verification as applied
to manufacturing systems and equipment, redefining the role of quality and streamlining
many of the repetitive and nonvalue added tasks in traditional commissioning
and qualification testing [15]. The standards for risk management and process under-
standing are close to approval, since any discussion over “regulatory flexibility” will be
commensurate with risk, and in proportion to the level of process understanding that has
been demonstrated, it will be helpful to share a common understanding of what those
terms mean with regulators.
ISPE has formed a PAT Community of Practice that serves as a forum to exchange
ideas and share approaches with other practitioners. The group organizes workshops and
meetings for training in PAT practices and issues, such as data management, regulatory
approaches, and business case for PAT. ISPE produces “Baseline Guides” to assist
members in meeting regulatory expectations for facilities and manufacturing equipment
and is in the process of revising the guide for Commissioning and Qualification to bring it
into alignment with the ASTM E2500 standard discussed earlier [15]. Education around
PAT was also seen as a priority, which led to the formation of the PAT Community of
Practice by ISPE. Furthermore, the Product Quality Lifecycle Implementation Initiative
was launched in 2007 to provide the technical framework for implementation of QbD and
to enable adoption of ICH Q8, Q9, and Q10 documents. Again, regulators are engaged
with ISPE communities of practice, which will ensure the continued development of
PAT and QbD approaches; none of this detracts from the earlier commitment to PAT.
The initial guidance was clear that the procedures would be “consistent with the basic
tenet of quality by design” [2].
